Transcripts of simian virus 41 (SV41) matrix gene are exclusively dicistronic with the fusion gene which is also transcribed as a monocistron

Tsurudome, Masato; Bando, Hideaki; Kawano, Mitsuo; Matsumura, Haruo; Komada, Hiroshi; Nishio, Machiko; Ito, Yasuhiko

doi:10.1016/0042-6822(91)90825-v

Cited by 25 publications

(20 citation statements)

References 24 publications

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“…In cells infected with WT SV5, ϳ40% of the F mRNA is detected by Northern blotting in an M-F dicistronic form (32). M-F readthrough transcription has been reported to be even higher in the case HPIV-2 (ϳ60%; Parks et al, unpublished), HPIV-1 (ϳ80% [4]), and SV41 (100% [43]). It is likely that each of these viruses has evolved a characteristic level of M-F readthrough transcription for optimal growth, but the effect on virus growth of altering this polymerase function has not been previously examined.…”

Section: Discussionmentioning

confidence: 97%

“…Readthrough transcription at most paramyxovirus gene junctions is relatively low, but the M-F junction is an exception to this rule for a number of viruses, including HPIV-1, -2, and -3, measles virus, SV41, and SV5 (4,6,29,39,43). In cells infected with WT SV5, ϳ40% of the F mRNA is detected by Northern blotting in an M-F dicistronic form (32).…”

Section: Discussionmentioning

confidence: 99%

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Increased Readthrough Transcription across the Simian Virus 5 M-F Gene Junction Leads to Growth Defects and a Global Inhibition of Viral mRNA Synthesis

Parks

Ward

Rassa

2001

J Virol

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Recombinant simian virus 5 (rSV5) mutants containing substitutions in the M-F intergenic region were generated to determine the effect of increased readthrough transcription on the paramyxovirus growth cycle. We have previously shown, using an SV5 dicistronic minigenome, that replacement of the 22-base M-F intergenic region with a foreign sequence results in a template (Rep22) that directs very high levels of M-F readthrough transcription. An rSV5 containing the Rep22 substitution grew slower and to final titers that were 50-to 80-fold lower than those of wild-type (WT) rSV5. Cells infected with the Rep22 virus produced very low levels of monocistronic M and F mRNA, consistent with the M-F readthrough phenotype. Surprisingly, Rep22 virus-infected cells also displayed a global decrease in the accumulation of viral mRNA from genes located upstream and downstream of the M-F junction, and overall viral protein synthesis was reduced. Second-site revertants of the Rep22 virus that had regained WT transcription and growth properties contained a single base substitution that increased the M gene end U tract from four to eight residues, suggesting that the growth defects originated from higher-than-normal M-F readthrough transcription. Thus, the primary growth defect for the Rep22 virus appears to be in viral RNA synthesis and not in morphogenesis. A second rSV5 virus (G14), which contained a different foreign M-F intergenic sequence, grew to similar or slightly higher titers than WT rSV5 in some cell types and produced ϳ1.5-to 2-fold more mRNA and viral protein. The data support the hypothesis that inhibition of Rep22 virus growth is due to increased access by the polymerase to the 5 end of the genome and to the resulting overexpression of L protein. We propose that the elevated naturally occurring M-F readthrough which is characteristic of many paramyxoviruses serves as a mechanism to fine-tune the level of polymerase that is optimal for virus growth.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Increased Readthrough Transcription across the Simian Virus 5 M-F Gene Junction Leads to Growth Defects and a Global Inhibition of Viral mRNA Synthesis

Parks

Ward

Rassa

2001

J Virol

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“…For Sendai virus (SeV), the GS signal of the F gene has a reduced efficiency, resulting in the reduced transcription of the F gene as well as of downstream genes (27). Interestingly, simian virus 41 completely lacks any apparent M-GE signal, and the M gene is transcribed exclusively as an M-F bicistronic mRNA with reduced monocistronic F transcription (26,28). HPIV1, on the other hand, has several cis-acting elements, including the M-F intergenic sequence, the F-GS signal, and a long upstream NTR in the F gene, which together attenuate M gene transcription termination, promote higher levels of M-F readthrough, and result in reduced expression levels of F protein in infected cells (29).…”

Section: Discussionmentioning

confidence: 99%

“…This results in reduced production of F protein in HPIV3-infected cells and reduced incorporation of F protein into HPIV3 virions. A number of related paramyxoviruses also appear to have various different mechanisms that have the common effect of downregulating the expression of the F gene (26)(27)(28)(29). In the case of HPIV3, this did not appear to have any effect on virus replication or pathogenicity.…”

Section: Discussionmentioning

confidence: 99%

The Aberrant Gene-End Transcription Signal of the Matrix M Gene of Human Parainfluenza Virus Type 3 Downregulates Fusion F Protein Expression and the F-Specific Antibody Response In Vivo

Lingemann

Surman

Amaro-Carambot

et al. 2015

J Virol

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Human parainfluenza virus type 3 (HPIV3), a paramyxovirus, is a major viral cause of severe lower respiratory tract disease in infants and children. The gene-end (GE) transcription signal of the HPIV3 matrix (M) protein gene is identical to those of the nucleoprotein and phosphoprotein genes except that it contains an apparent 8-nucleotide insert. This was associated with an increased synthesis of a readthrough transcript of the M gene and the downstream fusion (F) protein gene. We hypothesized that this insert may function to downregulate the expression of F protein by interfering with termination/reinitiation at the M-F gene junction, thus promoting the production of M-F readthrough mRNA at the expense of monocistronic F mRNA. To test this hypothesis, two similar recombinant HPIV3 viruses from which this insert in the M-GE signal was removed were generated. The M-GE mutants exhibited a reduction in M-F readthrough mRNA and an increase in monocistronic F mRNA. This resulted in a substantial increase in F protein synthesis in infected cells as well as enhanced incorporation of F protein into virions. The efficiency of mutant virus replication was similar to that of wild-type (wt) HPIV3 both in vitro and in vivo. However, the F-proteinspecific serum antibody response in hamsters was increased for the mutants compared to wt HPIV3. This study identifies a previously undescribed viral mechanism for attenuating the host adaptive immune response. Repairing the M-GE signal should provide a means to increase the antibody response to a live attenuated HPIV3 vaccine without affecting viral replication and attenuation. IMPORTANCEThe HPIV3 M-GE signal was previously shown to contain an apparent 8-nucleotide insert that was associated with increased synthesis of a readthrough mRNA of the M gene and the downstream F gene. However, whether this had any significant effect on the synthesis of monocistronic F mRNA or F protein, virus replication, virion morphogenesis, and immunogenicity was unknown. Here, we show that the removal of this insert shifts F gene transcription from readthrough M-F mRNA to monocistronic F mRNA. This resulted in a substantial increase in the amount of F protein expressed in the cell and packaged in the virus particle. This did not affect virus replication but increased the F-specific antibody response in hamsters. Thus, in wild-type HPIV3, the aberrant M-GE signal operates a previously undescribed mechanism that reduces the expression of a major neutralization and protective antigen, resulting in reduced immunogenicity. This has implications for the design of live attenuated HPIV3 vaccines; specifically, the antibody response against F can be elevated by "repairing" the M-GE signal to achieve higher-level F antigen expression, with no effect on attenuation.H uman parainfluenza viruses (HPIVs) are human respiratory tract pathogens present as four serotypes, namely, HPIV1, HPIV2, HPIV3, and HPIV4. HPIVs infect and cause respiratory illness in humans of all ages worldwide, but their greatest impact...

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“…Tsurudome et al (1990) have reported that the antigenic and structural properties of SV41 reveal a closer relationship to human parainfluenza type 2 virus (HPIV-2) than to simian virus 5 (SV5). The nucleotide sequence of the SV41 genome with the exception of the P gene has already been determined (Tsurudome et al, , 1991aOgawa et al, 1992).…”

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confidence: 99%

Sequence Determination of the P Gene of Simian virus 41: Presence of Irregular Deletions Near the RNA-Editing Sites of Paramyxoviruses

Kawano

Tsurudome

Oki

et al. 1993

Journal of General Virology

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The complete nucleotide sequence of the P gene of simian virus 41 (SV41) was determined. The gene was found to be 1406 nucleotides long and to contain a relatively small open reading frame encoding a cysteinerich V protein with a calculated M r of 24 076. We have demonstrated that RNA-editing events occur in SV41 P gene transcripts and that the ratio of edited mRNAs to faithfully copied mRNA (P-mRNA :V-mRNA) is about 1:5 at either 24 or 40 h post-infection. The mRNA with two G insertions was capable of encoding a P protein of 395 amino acids with a predicted M r of 41 992. A kinetic study of P and V proteins by Western blot analysis showed that in virus-infected cells the amounts of both proteins were almost equal although the V-mRNA was considerably more abundant than the P-mRNA. Alignment of the SV41 P and V proteins with those of nine other paramyxoviruses demonstrated that irregular gaps were present around the RNA-editing sites.

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Transcripts of simian virus 41 (SV41) matrix gene are exclusively dicistronic with the fusion gene which is also transcribed as a monocistron

Cited by 25 publications

References 24 publications

Increased Readthrough Transcription across the Simian Virus 5 M-F Gene Junction Leads to Growth Defects and a Global Inhibition of Viral mRNA Synthesis

Increased Readthrough Transcription across the Simian Virus 5 M-F Gene Junction Leads to Growth Defects and a Global Inhibition of Viral mRNA Synthesis

The Aberrant Gene-End Transcription Signal of the Matrix M Gene of Human Parainfluenza Virus Type 3 Downregulates Fusion F Protein Expression and the F-Specific Antibody Response In Vivo

Sequence Determination of the P Gene of Simian virus 41: Presence of Irregular Deletions Near the RNA-Editing Sites of Paramyxoviruses

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